Shifting genomes, rising threats: Adaptive evolution and antimicrobial resistance of E. coli ST10 across African ecologies.

Escherichia coli sequence type 10 (ST10) is an emerging zoonotic lineage with global distribution and a high antimicrobial resistance (AMR) burden, yet its population dynamics across Africa remain poorly understood. Here, we analysed 159 E. coli ST10 genomes including four newly sequenced isolates and 155 publicly available genomes from 19 African countries spanning human, animal, food, and environmental sources. Whole genome sequencing revealed high species-level similarity (mean average nucleotide identity: 99.44%), but single nucleotide polymorphism (SNP)-based phylogenetics delineated 122 distinct clusters, indicating substantial intra-lineage diversity. Over 71% of isolates were multidrug-resistant, with 29% carrying the extended-spectrum β-lactamase gene bla_CTX-M-15. Plasmid replicon analysis highlighted the widespread presence of IncFIB and ColRNAI plasmids, strongly linked to AMR gene carriage. Human-derived isolates predominated both phylogenetic clusters and resistance profiles. SNP-based comparisons revealed evidence of both localized evolution and long-distance dissemination across countries. These interconnected pathways underscore the bacterium's ecological ubiquity and the limitations of siloed surveillance strategies. The predominance of human-derived isolates and evidence of both local and cross-border transmission highlight humans as key reservoirs and underscore the need for coordinated surveillance. These findings underscore the urgent need for integrated continent-wide One Health approach strategies to monitor and combat antimicrobial resistance, economic impact on trade restrictions and health security threats.